ALLERGEN GENE VACCINATION IN MOUSE MODEL OF FOOD ALLERGY

描述：申请人安东尼·霍纳博士是一名助理临床医生。 加州大学圣地亚哥分校的儿科学教授。Dr。 霍纳在波士顿儿童医院接受过敏和免疫学培训 1991-1994年，他在Raif Geha博士的指导下研究CD40配体(CD40L)。 他于1994年来到加州大学圣迭戈分校，直到最近还在继续研究CD40L。戴维斯博士。 埃亚尔·拉兹和丹尼斯·卡森担任申请者的导师。Dr。 金·巴雷特将担任顾问/合作者。 申请者对这个项目的目标是(1)获得更多的实验室 分子生物学领域的技能和动物模型的使用 过敏性疾病，(2)进一步发展他作为一个 内科科学家，以及(3)创建卓越中心 加州大学圣迭戈分校食物过敏的诊断和处理。 申请人建议探索质粒DNA(PDNA)的潜力 免疫抑制和逆转Th2介导的变态反应性 口服抗原。他将使用已建立的小鼠模型 口腔过敏和过敏反应的特征是对 Th2介导的免疫应答：(1)皮内过敏原基因疫苗 同时编码变应原和免疫刺激(IS)序列的PDNA和(2) 皮内联合注射天然蛋白和单一结构域是 序列丰富的pDNA。然后，申请者将描述细胞的特征 疫苗接种所需的免疫反应的组成部分 Th1介导的免疫的发展和维持及排除 Th2介导的过敏反应。

DESCRIPTION: The applicant, Dr. Anthony Horner, is an assistant clinical professor of pediatrics at the University of California at San Diego. Dr. Horner trained in allergy and immunology at Boston Children's Hospital from 1991 - 1994, where he studied the CD40 ligand (CD40L) under Dr. Raif Geha. He came to UCSD in 1994 and until recently continued to work on CD40L. Drs. Eyal Raz and Dennis Carson are serving as mentors for the applicant. Dr. Kim Barrett will serve as a consultant/collaborator. The applicant's goals for this project are (1) to acquire further laboratory skills in the area of molecular biology and the use of animal models of allergic disease, (2) to further develop his intellectual skills as a physician scientist, and (3) to create a center of excellence for the diagnosis and management of food allergies at UCSD. The applicant proposes to explore the potential of plasmid DNA (pDNA) immunization to inhibit and reverse Th2-mediated allergic hypersensitivity to orally administered antigen. He will use an established mouse model of oral allergy and anaphylaxis to characterize protection against a Th2-mediated response by (1) intra-dermal allergen gene vaccination using pDNA encoding both allergen and immunostimulatory (IS) sequences and (2) intra-dermal co-injection of native protein plus single domain IS sequence-enriched pDNA. The applicant will then characterize the cellular components of the immune response to vaccination which are required for the development and maintenance of Th1-mediated immunity and the exclusion of Th2-mediated allergic hypersensitivity.